Total synthesis of (−)-dictyostatin, a microtubule-stabilising anticancer macrolide of marine sponge origin

An efficient convergent synthesis of the anticancer marine macrolide (−)-dictyostatin is described that proceeds in 4.6% yield over 27 steps. Most of the stereocentres were configured using substrate control, making use of a common building block to install the C12–C14 and C20–C22 stereotriads, with a lactate boron aldol reaction employed to construct a C4–C10 β-ketophosphonate as utilised in the pivotal Still–Gennari HWE coupling step with a fully elaborated C11–C26 aldehyde. Following introduction of the (2Z,4E)-dienoate, a modified Yamaguchi macrolactonisation and deprotection delivered the requisite 22-membered macrocyclic lactone.